Novel laminate structures, collection assemblies, and autosensor assemblies for use in a sampling device are described. The invention relates generally to consumable components of a device used for continually or continuously measuring the concentration of target chemical analytes present in a biological system. The laminates, collection assemblies, and autosensor assemblies are used in a transdermal sampling device that is placed in operative contact with a skin or mucosal surface of a biological system to obtain a chemical signal associated with an analyte of interest.
A number of diagnostic tests are routinely performed on humans to evaluate the amount or existence of substances present in blood or other body fluids. These diagnostic tests typically rely on physiological fluid samples removed from a subject, either using a syringe or by pricking the skin. One particular diagnostic test entails self-monitoring of blood glucose levels by diabetics.
Diabetes is a major health concern, and treatment of the more severe form of the condition, Type I (insulin-dependent) diabetes, requires one or more insulin injections per day. Insulin controls utilization of glucose or sugar in the blood and prevents hyperglycemia which, if left uncorrected, can lead to ketosis. On the other hand, improper administration of insulin therapy can result in hypoglycemic episodes, which can cause coma and death. Hyperglycemia in diabetics has been correlated with several long-term effects of diabetes, such as heart disease, atherosclerosis, blindness, stroke, hypertension and kidney failure.
The value of frequent monitoring of blood glucose as a means to avoid or at least minimize the complications of Type I diabetes is well established. Patients with Type II (non-insulin-dependent) diabetes can also benefit from blood glucose monitoring in the control of their condition by way of diet and exercise.
Conventional blood glucose monitoring methods generally require the drawing of a blood sample (e.g., by finger prick) for each test, and a determination of the glucose level using an instrument that reads glucose concentrations by electrochemical or colorimetric methods. Type I diabetics must obtain several finger prick blood glucose measurements each day in order to maintain tight glycemic control. However, the pain and inconvenience associated with this blood sampling, along with the fear of hypoglycemia, has led to poor patient compliance, despite strong evidence that tight control dramatically reduces long-term diabetic complications. In fact, these considerations can often lead to an abatement of the monitoring process by the diabetic. See, e.g., The Diabetes Control and Complications Trial Research Group (1993) New Engl. J. Med. 329:977-1036.
Recently, various methods for determining the concentration of blood analytes without drawing blood have been developed. For example, U.S. Pat. No. 5,267,152 to Yang et al. describes a noninvasive technique of measuring blood glucose concentration using near-IR radiation diffuse-reflection laser spectroscopy. Similar near-IR spectrometric devices are also described in U.S. Pat. No. 5,086,229 to Rosenthal et al. and U.S. Pat. No. 4,975,581 to Robinson et al.
U.S. Pat. Nos. 5,139,023 to Stanley et al., and 5,443,080 to D""Angelo et al. describe transdermal blood glucose monitoring devices that rely on a permeability enhancer (e.g., a bile salt) to facilitate transdermal movement of glucose along a concentration gradient established between interstitial fluid and a receiving medium. U.S. Pat. No. 5,036,861 to Sembrowich describes a passive glucose monitor that collects perspiration through a skin patch, where a cholinergic agent is used to stimulate perspiration secretion from the eccrine sweat gland. Similar perspiration collection devices are described in U.S. Pat. No. 5,076,273 to Schoendorfer and U.S. Pat. No. 5,140,985 to Schroeder.
In addition, U.S. Pat. No. 5,279,543 to Glikfeld et al. describes the use of iontophoresis to noninvasively sample a substance through skin into a receptacle on the skin surface. Glikfeld teaches that this sampling procedure can be coupled with a glucose-specific biosensor or glucose-specific electrodes in order to monitor blood glucose. Finally, International Publication No. WO 96/00110, published Jan. 4, 1996, describes an iontophoretic apparatus for transdermal monitoring of a target substance, wherein an iontophoretic electrode is used to move an analyte into a collection reservoir and a biosensor is used to detect the target analyte present in the reservoir. Finally, International Publication No. WO 96/00110 to Tamada describes an iontophoretic apparatus for transdermal monitoring of a target substance, where an iontophoretic electrode is used to move an analyte into a collection reservoir and a biosensor is used to detect the target analyte present in the reservoir.
The present invention relates generally to collection assembly, laminates and autosensor assemblies for use in a sampling device. More particularly, the present collection assembly, laminates and autosensor assemblies are used in a transdermal sampling device that is placed in operative contact with a skin or mucosal surface of the biological system to obtain a chemical signal associated with an analyte of interest. The sampling device transdermally extracts the analyte from the biological system using, for example, an iontophoretic sampling technique. The transdermal sampling device can be maintained in operative contact with the skin or mucosal surface of the biological system to provide, for example, continual or continuous analyte measurement.
The analyte can be any specific substance or component that one is desirous of detecting and/or measuring in a chemical, physical, enzymatic, or optical analysis. The analyte can be any specific substance or component that one is desirous of detecting and/or measuring in a chemical, physical, enzymatic, or optical analysis. Such analytes include, but are not limited to, amino acids, enzyme substrates or products indicating a disease state or condition, other markers of disease states or conditions, drugs of abuse, therapeutic and/or pharmacologic agents (e.g., theophylline, anti-HIV drugs, lithium, anti-epileptic drugs, cyclosporin, chemotherapeutics), electrolytes, physiological analytes of interest (e.g., urate/uric acid, carbonate, calcium, potassium, sodium, chloride, bicarbonate (CO2), glucose, urea (blood urea nitrogen), lactate/lactic acid, hydroxybutyrate, cholesterol, triglycerides, creatine, creatinine, insulin, hematocrit, and hemoglobin), blood gases (carbon dioxide, oxygen, pH), lipids, heavy metals (e.g., lead, copper), and the like. In preferred embodiments, the analyte is a physiological analyte of interest, for example glucose, or a chemical that has a physiological action, for example a drug or pharmacological agent.
Thus, one embodiment of the invention provides a tri-layer collection assembly for use in a transdermal sampling device. The collection assembly is formed from a series of functional layers including: (1) a first surface layer that is comprised of a substantially planar material that has an opening which extends therethrough; (2) a second surface layer that is also comprised of a substantially planar material and has an opening therein; and (3) an intervening layer that is positioned between the first and second surface layers, wherein the intervening layer is comprised of an ionically conductive material. The first and second surface layers overlap the intervening layer at corresponding positions, and contact each other at their corresponding overlaps, such overlaps can be used to form a laminate structure. The openings in the first and second surface layers are axially aligned to provide a flow path through the laminate (i.e., a flow path that extends between the two surfaces and passes through the intervening layer). The overhangs provided by the mask and retaining layers are generally contacted with each other to sandwich the collection insert therebetween and form the assembly.
It is a related object of the invention to provide an autosensor assembly for use in a transdermal sampling device, wherein the assembly comprises the three functional layers of the above-described collection assembly or laminate, an electrode assembly, and, typically, a support tray.
It is a further object of the invention to provide a two layer collection assembly or laminate for use in a transdermal sampling device. The collection assembly is formed from two functional layers including: (1) a surface layer that is comprised of a substantially planar material that has an opening which extends therethrough; and (2) a second layer. The second layer is formed from the combination of a gasket and a collection insert. The gasket is comprised of a substantially planar material having a top face, a bottom face, and an opening extending between the top and bottom faces. The top face of the gasket is attached to the bottom face of the surface layer, and the opening in the gasket is axially aligned with the opening in the surface layer to provide a flow path through the laminate. The collection insert is arranged within and substantially fills the opening in the gasket such that the collection insert is aligned with the opening in the surface layer and rests against or is otherwise attached to a portion of the surface layer.
It is a related object of the invention to provide an autosensor assembly for use in a transdermal sampling device, wherein the assembly comprises the two layers of the above-described collection assembly or laminate, an electrode assembly with which the collection assembly is functionally aligned, and, typically, a support tray.
Thus, in one embodiment, the invention relates to a collection assembly for use in a iontophoretic sampling device useful to monitor a selected analyte or derivatives thereof present in a biological system. The collection assembly comprises:
a) a collection insert layer comprised of an ionically conductive material having first and second portions, each portion having first and second surfaces,
b) a mask layer comprised of a material that is substantially impermeable to the selected analyte or derivatives thereof, wherein the mask layer (i) has inner and outer faces and said outer face provides contact with said biological system and the inner face is positioned in facing relation with the first surface of each collection insert, (ii) defines first and second openings that are aligned with the first and second portions of the collection insert layer, (iii) each opening exposes at least a portion of the first surface of the collection insert layer, and (iv) has a border which extends beyond the first surface of each portion of the collection insert layer to provide an overhang; and
(c) a retaining layer having (i) inner and outer faces wherein the inner face is positioned in facing relation with the second surface of each collection insert, (ii) defines first and second openings that are aligned with the first and second portions of the collection insert layer, (iii) each opening exposes at least a portion of the second surface of the collection insert layer, and (iv) has a border which extends beyond the first surface of each portion of the collection insert layer to provide an overhang.
In certain embodiments, the collection insert layer further comprises a gasket layer and the gasket layer is between the mask layer and the retaining layer.
In additional embodiments, the subject invention is directed to a laminate comprising a collection assembly, as described above, as well as a sealed package containing the laminate.
In still another embodiment, the invention is directed to an autosensor assembly for use in a iontophoretic sampling device useful to monitor an analyte present in a biological system. The autosensor assembly comprises:
(I) a collection assembly which comprises,
a) a collection insert layer comprised of an ionically conductive material having first and second portions, each portion having first and second surfaces,
b) a mask layer comprised of a substantially planar material that is substantially impermeable to the selected analyte or derivatives thereof, wherein the mask layer (i) has inner and outer faces and the outer face provides contact with the biological system and the inner face is positioned in facing relation with the first surface of each collection insert, (ii) defines first and second openings that are aligned with the first and second portions of the collection insert layer, (iii) each opening exposes at least a portion of the first surface of the collection insert layer, and (iv) has a border which extends beyond the first surface of each portion of the collection insert layer to provide an overhang;
(c) a retaining layer having (i) inner and outer faces wherein the inner face is positioned in facing relation with the second surface of each collection insert, (ii) defines first and second openings that are aligned with the first and second portions of the collection insert layer, (iii) each opening exposes at least a portion of the second surface of the collection insert layer, and (iv) has a border which extends beyond the first surface of each portion of the collection insert layer to provide an overhang; and
(d) where the first and second openings in the mask layer are positioned in the collection assembly such that they are aligned with the first and second openings in the retaining layer and thereby define a plurality of flow paths through said collection assembly;
(II) an electrode assembly having an inner and outer face, the inner face comprising first and second bimodal electrodes, wherein the first and second bimodal electrodes are aligned with the first and second openings in the retaining layer of the collection assembly; and
(III) a support tray that contacts the outer face of the electrode assembly.
In alternative embodiments, the autosensor assembly further comprises a first removable liner attached to the outer face of the retaining layer, and/or a second removable liner attached to the outer face of the mask layer. In addition, a plowfold liner can be used, for example, between the electrode surfaces and the collection inserts.
In further embodiments, the invention is directed to a sealed package containing the autosensor assembly described above. The sealed package may also contain a hydrating insert.
In yet another embodiment, the invention is directed to a collection assembly for use in a iontophoretic sampling device useful to monitor a selected analyte, or derivatives thereof, present in a biological system. The collection assembly comprises:
a) a mask layer comprised of a substantially planar material that is substantially impermeable to the selected analyte or derivatives thereof, where the mask layer has inner and outer faces and the outer face provides contact with the biological system;
b) a collection insert layer comprised of an ionically conductive material having first and second surfaces, and
c) the mask and collection insert layers are configured such that (i) at least a portion of the collection insert is exposed to provide contact with the biological system, and (ii) flow of the analyte through the first surface of the collection insert layer from the biological system is prevented by the mask layer for any portion of the first surface of the collection insert layer that is in contact with the inner face of the mask layer.
In another embodiment, the invention is directed to an autosensor assembly comprising
(a) the collection assembly above,
(b) an electrode assembly having an inner face comprising an electrode and an outer face, where the inner face of the electrode assembly and the collection assembly are aligned to define a plurality of flow paths through the collection assembly, and
(c) a support tray that contacts the outer face of the electrode assembly.
Additional objects, advantages and novel features of the invention will be set forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination of the following, or may be learned by practice of the invention.